Telavancin: a lipoglycopeptide antimicrobial for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria in adults.

摘要

BACKGROUND: Telavancin, a lipoglycopeptide antibiotic, is a semisynthetic derivative of vancomycin. It was approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. OBJECTIVE: This article summarizes the pharmacology, in vitro and in vivo activity, pharmacokinetic properties, and clinical efficacy and tolerability of telavancin. METHODS: Relevant information was identified through a search of MEDLINE (1966-August 2010), Iowa Drug Information Service (1966-August 2010), International Pharmaceutical Abstracts (1970-August 2010), and Google Scholar using the terms telavancin, lipoglycopeptide, and TD-6424. Abstracts and posters from scientific meetings, as well as documents submitted by the manufacturer of telavancin to the FDA as part of the approval process, were consulted. In vivo and in vitro experimental and clinical studies and review articles that provided information on the activity, mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of telavancin were reviewed. RESULTS: In vitro, telavancin has potent activity against S aureus, including methicillin-resistant strains; Streptococcus pneumoniae; and vancomycin-susceptible enterococci with MICs generally <1 mug/mL. Telavancin appears to have a dual mechanism of action, inhibiting cell wall formation and disrupting the cell membrane. In Phase III studies (ATLAS 1 and ATLAS 2), telavancin was found to be noninferior to vancomycin, with clinical cure rates of 88.3% and 87.1%, respectively, in clinically evaluable patients in the treatment of cSSSIs (difference, 1.2%; 95% CI, -2.1 to 4.6; P = NS). The effectiveness of telavancin in the treatment of hospital-acquired pneumonia was assessed in 2 Phase III studies (ATTAIN 1 and ATTAIN 2). Preliminary findings were that the effectiveness of telavancin was not significantly different from that of vancomycin, with cure rates of 82.7% and 80.9% in the clinically evaluable population, respectively (difference, 1.8%; 95% CI, -4.1 to 7.7; P = NS). The most commonly (>10%) reported adverse events included taste disturbances, nausea, headache, vomiting, foamy urine, constipation, and insomnia. CONCLUSION: In clinical trials, the effectiveness of telavancin was not significantly different from that of vancomycin in the treatment of cSSSIs, and telavancin was generally well tolerated.